[unreadable] This is an application for renewal of a Research Scientist Award (K05) to Dr. Sam A. Deadwyler, Professor of Physiology, Wake Forest University School of Medicine. The objectives of the research over the next five years of the award are delineated in the Research Plan and cover five related research projects, each supported by a separate individual research grant. The four areas include: 1) effects of cannabinoids on hippocampal memory processes; 2) tolerance to the effects of cannabinoids on memory; 3) neurophysiological assessment of cocaine self-administration; 4) recording in nonhuman primates and 5) implementation of genomic profiling. These five research areas have been under investigation during the last award period. Each of the grants supporting that research is currently active. The overall strategy of the research proposed is to understand at the cellular and molecular level the effects of cannabinoids and cocaine on neural substrates of behavior. With respect to cannabinoids, both the endogenous and exogenous cannabinoid (CB1) receptor ligands will continue to be assessed regarding their influence on memory processes mediated via the hippocampus. In addition, investigations of the chronic effects of these substances will determine the cellular and genetic mechanisms of tolerance in the cannabinoid system in the brain. The third area of study focuses on the effects of cocaine on neurons located in the nucleus accumbens (NAc), an area of the brain believed to be critical for establishing and maintaining reinforced behaviors. Specifically, these studies will continue to investigate the firing patterns of neurons in the NAc in animals self-administering cocaine. Finally, new areas of investigation include gene microarray profiling in the above experimental paradigms, and the extension of the above electrophysiological investigations to nonhuman primates. The renewal of this award will allow Dr. Deadwyler to continue to devote maximal effort to the above research objectives, freeing him from other departmental and teaching responsibilities. It will also provide him with the opportunity to expand his research on the above topics to include more advanced techniques and to continue collaborations with other well-known researchers in the field on topics of mutual interest. [unreadable] [unreadable] [unreadable] [unreadable]